Basis for Efficacy and Failure of Vaccines

It seems so simple. Just give your horse a few jabs every spring and you've taken care of all those nasty diseases – tetanus, influenza, Potomac Horse Fever, strangles. Is it really so simple? No, is the resounding answer. Vaccination is a complex and tricky business. In essence, we are trying to fool Mother Nature – and that can be a difficult thing to do indeed. We're trying to convince the horse's immune system that it has already seen and successfully fought off a disease without ever becoming sick.

The Immune System Made Simple

There are two major parts of the immune system: the humoral, or blood borne portion, and the cellular portion. Both of these portions of the immune system rely on being able to distinguish between self and non-self, or foreign. Both the humoral and the cellular system do this by recognizing portions of foreign molecules (termed antigens). Most people have heard of antibodies – these are the keystone of the humoral immune system, which is most effective against bacteria. The antibody is a molecule that recognizes a unique part of the pathogen, and effectively docks with the pathogen. Once this portion of the virus or bacteria is covered with antibody, other parts of the immune system – such as inflammatory cells – can now recognize the invader as being foreign, and rush in to kill it. The cellular immune system also recognizes specific antigens, but it is most important for defense against invaders such as fungi, protozoa and viruses.

Both parts of the immune system rely on a process termed anamnesis, or memory. The first time that the immune system is called upon to make antibodies against bacteria A, for instance, it takes a while to get production going. The second, and perhaps third time that the immune system must make those antibodies, the production line is ready – and the response occurs very quickly. This is termed the anamnestic response. This is why most vaccines must given more than once in order for the animal to be properly vaccinated.

There are two major requirements for an effective vaccine. Remember that we are trying to prompt the specific arm of the immune system to get "geared up" for an attack by specific pathogens at some unknown time in the future. First, and foremost, the immune system needs to recognize the vaccine as being foreign – not self. Secondly, the vaccine must not actually cause disease. The very first vaccines were rather crude – a doctor recognized that milkmaids from the country tended to have beautiful complexions, because they tended not to get smallpox – a disease that either disfigured or killed its victims. He cleverly deduced that it was because the milkmaids were exposed to cowpox – which had much less virulent effects on people. The cowpox caused their immune systems to respond with an antibody that recognized not just cowpox, but also smallpox.

The biggest distinction among vaccines is killed versus modified live, or attenuated. The first smallpox vaccine was, in a way, a modified live vaccine – it needed to replicate in the body to elicit a strong immune response, but it was able to do that without causing disease. Today, live vaccines are still produced by weakening the pathogen in some way, while still allowing it to replicate in the host's body. Killed vaccines are exactly as they sound – no portion of the pathogen is alive and able to cause disease. Rather, the dead pathogen, or portions of it, are able to elicit an immune response merely by their presence. They are usually combined with an adjuvant – a molecule that non-specifically helps the immune system to respond to the vaccination.

There are a variety of reasons why a vaccine may fail and the horse becomes ill. Some of the more common causes are:

• Improper storage. Many vaccines are live vaccines and are actually quite delicate when they are outside the body, and can die when they are exposed to heat or sun.
• Vaccine is not effective against all forms of a single virus. Your horse can't mount an immune response to a pathogen unless that vaccine is actually given. Surprisingly enough – people doing their horse's vaccinations on their own have been known to forget the really important ones – like tetanus toxoid. In some cases, vaccines for certain manifestations of disease simply don't exist. For example, we do have a fairly good vaccine against the respiratory form of herpes virus (Rhinopneumonitis). However, the same virus strain causes neurological disease, but vaccines do not protect against this form.
• You did not give enough time or amount of the vaccine to work. Proper vaccination relies on a good anamnestic response. Even the manufacturer's recommendations do not always ensure that this will happen. Recent studies have shown that many vaccines require more booster shots than the number recommended on the label in order to get a really good anamnestic response. The minimum number of booster shots for most vaccines is two, but many will give a far more effective response if boosters are given three times.
• The vaccine or its adjuvant are weak. The government has certain requirements that must be met for a vaccine to be approved for use. Logically, it seems as though the most important requirement should be that the vaccine is efficacious and safe– that is, it can prevent disease in horses that are vaccinated without making them sick.

It is also important to consider how common a disease is when assessing vaccine efficacy. If only 1 percent of the equine population gets the disease under natural circumstances, it will be tremendously difficult to determine if a vaccine will protect that population – few if any vaccines will be 99 percent efficacious. For example, although EPM and Potomac Horse Fever cause a lot of worry in horse owners, they are actually quite uncommon – and so it will be difficult to determine if your horse is being protected or not. Recent studies showed that horses in New York State, vaccinated in accordance with the label, were not adequately protected against the disease. Experienced veterinarians generally feel that more frequent vaccinations (every 3 to 4 months) do help to protect the horse.

• The horse comes across a new strain of virus after vaccination. Some pathogens, especially viruses, have become "successful" by being able to change their antigenicity. This means that they are able to switch the proteins that they produce – the very proteins that your horse's immune system has been primed to recognize. Equine influenza is notorious for being able to do this. There are many strains of influenza, and new ones are continually cropping up. Perhaps the horse has been vaccinated as often as every 3 months against influenza; but if the vaccine contains a strain different to the one your horse was exposed to, then the response will be useless in repelling the invader.
• The horse mounts the wrong type of immune response. Although we have talked primarily about the antibody response, antibodies are not always the best way to attack an invader. If the invader is not a typical bacteria but, rather, is a protozoal organism (as is the case with EPM), then antibodies are useful as a marker of exposure to disease, but are not very useful at all in fighting disease. Rather, a cell-mediated response is required. It is difficult to produce with vaccines, and very difficult to assess.

Sometimes the wrong type of antibody is produced. For example, the antibodies that fight disease at mucosal surfaces, such as the lining of the nose, are called IgA. The antibodies that fight disease at the level of the tissue are called IgG. Most vaccines are given by intramuscular injection and stimulate the production of IgG. If, as with strangles and influenza, the disease is transmitted at the mucosal level, a vaccine that stimulates IgA will be more effective (as with the intranasal vaccines against these diseases).

• Individual inability to mount immune response. The individual animal contributes greatly to how well a vaccine works. First, is your horse healthy? If your horse is busy fighting some other disease, he may not be able to put up a good response to a vaccine. Second, is your horse being treated with any immune suppressive drugs, such as corticosteroids? If your horse has had an allergic skin or respiratory problem in the recent past, chances are, he may have been on one of these drugs. Finally, what age is your horse? If he is a youngster, then he may still have a lot of maternal antibody in his system – this is antibody that he acquired through his mother's colostrum. It will eventually disappear, but while there is a high level of it in his blood (up to 4 or even 6 months of age) it will in many cases completely block your horse's own immune system from making a response to even the best of vaccines.